Hormonal modulation of Ishikawa cells during three-dimensional growth in vitro.

OBJECTIVES: The Ishikawa endometrial cancer cell line is hormonally responsive, expressing estrogen and progesterone receptors (ER, PR) when grown in traditional monolayer culture. The purpose of this paper is to demonstrate a three-dimensional spheroid culture system for cancer cells. We used this system to determine the response of the Ishikawa cell line to estradiol-17 beta (E), tamoxifen (T), megestrol acetate (MA), and progesterone (P). METHODS: Ishikawa cells were incubated in polyurethane culture bags using phenol red-free media containing ethanol (0.1%, controls), E (1 mumol, or 1 nmol), T (1 mumol, or 10 nmol), MA (1 mumol, or 10 nmol), or P (1 mumol). Cellular morphology was assessed by hematoxylin and eosin staining, and expression of estrogen and progesterone receptors was determined immunohistochemically using an immunoperoxidase technique. RESULTS: Cells in control cultures demonstrated minimal organization and lacked hormone receptors. In contrast, cells exposed to either E or T displayed significant glandular formation, with multicellular, microvilli-rich, columnar epithelia exhibiting polarized nuclear arrangements. Within 4 weeks, E- and T-treated cultures showed upregulated nuclear staining for PR, with little ER present. Cells treated with MA or P showed less glandular organization but expressed ER with PR downregulation. CONCLUSIONS: These data support the use of this novel three-dimensional culture system to study the modulation of tumor cell biologic activity in response to hormonal agents. Future applications of this model include examining in vitro responsiveness of cancer cell lines to additional biologic agents and chemotherapeutic regimens.

Maternal death from postpartum necrotizing fasciitis arising in an episiotomy: a case report.

BACKGROUND: Necrotizing fasciitis is a rare condition. We report a fatal case arising from an episiotomy in a previously healthy woman. CASE: A healthy 23-year-old prima gravida white female underwent vaginal delivery with repair of a proctoepisiotomy. Eighty-four hours postpartum, she developed increasing perineal swelling with severe pain. She presented on the 4th postpartum day with edema, erythema localized to the perineum, and vital signs significant only for tachycardia of 120/min. With a leukocytosis of 45,000/mul (87%) neutrophils, she was admitted to the hospital with an initial diagnosis of perineal cellulitis and empirically started on broad-spectrum intravenous antibiotic therapy. The patient's condition continued to deteriorate and she was then transferred to our facility on postpartum day 9 where a team performed two radical debridements of all necrotic tissue. Despite this and a broadened antibiotic coverage, the patient eventually experienced cardiopulmonary arrest and died on postpartum day 12. CONCLUSION: Necrotizing fasciitis must be considered in the differential diagnosis of the postpartum patient presenting with severe vulvar pain and erythema. Our patient exemplifies the obscure presentation with seemingly minimal skin changes. Any delay in diagnosis and treatment, which must include expeditious aggressive surgical debridement, will likely result in severe morbidity or mortality.

Chemotherapy plus sequential hormonal therapy for advanced and recurrent endometrial carcinoma: a phase II study.

We evaluated the therapeutic value of sequential cyclical hormonal therapy (megestrol acetate, and tamoxifen citrate) plus single-agent chemotherapy (carboplatin) in the outpatient management of advanced or recurrent endometrial cancer. Carboplatin (300 mg/m2) was administered every 4 weeks for six courses or until disease progression. In addition, patients alternated megestrol acetate (80 mg orally twice daily) with tamoxifen citrate (20 mg orally twice daily) every 3 weeks. Thirteen of 18 (72.2%) patients were considered evaluable. Four patients (30.8%) had a complete response, six (46.2%) had a partial response, one (7.7%) had stable disease, and two patients (15.4%) progressed. Six of seven patients with vaginal disease responded. The median progression-free interval was 14 months for complete responders. Two patients (15.4%) are alive with no evidence of disease at 41 and 59 months. Seven of 13 patients experienced a hematologic toxicity (six grade 2, one grade 3); all resolved within 2 weeks. Dose reduction of carboplatin to 200 mg/m2 was required in one patient. No other toxicities were encountered. The median survival for all patients is 11 months, and is 33 months for complete responders. We conclude that a regimen of carboplatin plus sequential hormonal therapy shows promise in this pilot study for the treatment of advanced or recurrent endometrial cancer.

Externalized Groshong catheters and Hickman ports for central venous access in gynecologic oncology patients.

There is a demand on gynecologic oncology services for semipermanent cannulization of central veins to improve the quality of life in cancer patients by circumventing the need for frequent peripheral venous punctures. Central venous thrombosis and sepsis are the major complications with these lines. We reviewed our experience with the externalized Groshong catheters and subcutaneously implanted Hickman ports in 104 gynecologic oncology patients requiring either chemotherapy (56), hyperalimentation (5), or supportive care (43). All devices were inserted under the supervision of one primary gynecologic oncologist. Groshong catheters and Hickman ports remained in place for a median of 68.5 and 210 days, respectively (P < 0.001). Thrombosis occurred in association with 4.8% of catheters and was exclusive to the Groshong catheters. Line sepsis occurred in 32% of Groshong catheters and 16.2% of Hickman ports (P = 0.04). Infection rates were not higher in dual-lumen compared to single-lumen Groshong catheters. Staphylococcus epidermidis was the comments isolate in line infections. The majority of lines were salvaged despite infectious complications. Malfunction of the catheter was equally common in both groups (10.5-13.5%), but was complete, necessitating replacement of only 2.9% of lines. The Groshong catheters took less time to insert (P < 0.003). The externalized Groshong catheter remains a useful alternative to the subcutaneously implanted ports, especially when relatively short-term use is anticipated, but gynecologic oncologists should be aware that there is an increased frequency of complications with the externalized catheter.

Laser vaporization for vulvar intraepithelial neoplasia III.

Eighteen women with vulvar intraepithelial neoplasia (VIN) III were treated with laser vaporization. The majority had multifocal disease. After a single laser vaporization, 15 of the 18 remained free of recurrent disease, with a mean follow-up of 129.5 weeks (range, 24-253). There were no intraoperative complications. Two patients had delayed healing and persistent vulvar soreness for 4 and 10 months. Laser vaporization appears to be reasonably well tolerated and effective for VIN III, especially multifocal.